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INCREASED CIRCULATING MATRIX GLA PROTEIN IN HEART FAILURE-ASSOCIATION WITH FUNCTIONAL, HEMODYNAMIC AND NEUROHORMONAL DISEASE SEVERITY
A25.E238 JACC March 9, 2010 Volume 55, issue 10A
CARDIAC FUNCTION AND HEART FAILURE INCREASED CIRCULATING MATRIX GLA PROTEIN IN HEART FAILURE-ASSOCIATION WITH FUNCTIONAL, HEMODYNAMIC AND NEUROHORMONAL DISEASE SEVERITY ACC Poster Contributions Georgia World Congress Center, Hall B5 Sunday, March 14, 2010, 3:30 p.m.-4:30 p.m.
Session Title: Myocardial Function/Heart Failure---Basic/Molecular Abstract Category: Myocardial Function/Heart Failure---Basic/Molecular Presentation Number: 1070-73 Authors: Thor Ueland, Christen P. Dahl, Lars Gullestad, Pal Aukrust, Sven Aakhus, Kaspar Broch, Cees Vermeer, Leon J. Schurgers, Oslo University Hospital, Oslo, Norway, Maastricht University, Maastricht, The Netherlands Background: Matrix gla protein (MGP) is a calcification-inhibitor and MGP-deficient mice develop extensive vascular calcification resulting in severe hemodynamic changes and early death from congestive heart failure (HF). Moreover, MGP could contribute to myocardial remodelling through “calcification-independent” mechanisms such as their effects on matrix remodelling. We hypothesized that patients with chronic HF would have dysregulated circulating MGP levels. Methods: We investigated circulating (by enzyme immunoassay) uncarboxylated MGP (dp-ucMGP) in patients with HF and investigated associations with clinical and biochemical measures of HF as well as associations with mortality/HTx. Results: Plasma dp-ucMGP was markedly increased in patients (n=181) compared to healthy controls (n=92) with increasing levels according to etiology (increased in ischemic disease, p=0.004) and functional (NYHA, p=0.001), hemodynamic (correlation LVEF, r=-0.25, p=0.002; WMSI, r=0.28, p=0.001), and neurohormonal disease severity (correlation NTproBNP, r=0.40, p<0.001). Further, when investigating associations with mortality, non-survivors or patients who underwent HTx during a follow-up of 3.1±1.5 (mean±SD) years, had increased plasma levels compared to survivors (p=0.043). Survival analysis revealed a significantly higher mortality/HTx rate in the highest quartile of dp-ucMGP [HR 1.85 (1.01-3.38), p=0.045]. The activation of MGP is highly vitamin K dependent and adjusting for the use of vitamin K antagonists in multi-variable analyses, with dpucMGP as a continuous variable, still revealed predictive information for risk estimation. However, no predictive information for the risk estimation of was observed beyond demographic, clinical and biochemical variables (LVEF, NYHA class, etiology, age, sex, previous infarction, serum creatinine, LDL cholestrol and NTproBNP). Conclusion: Our data suggest a potential role for dp-ucMGP in the development of left ventricular dysfunction that should be further investigated.
CARDIAC FUNCTION AND HEART FAILURE INCREASED CIRCULATING MATRIX GLA PROTEIN IN HEART FAILURE-ASSOCIATION WITH FUNCTIONAL, HEMODYNAMIC AND NEUROHORMONAL DISEASE SEVERITY ACC Poster Contributions Georgia World Congress Center, Hall B5 Sunday, March 14, 2010, 3:30 p.m.-4:30 p.m.
Session Title: Myocardial Function/Heart Failure---Basic/Molecular Abstract Category: Myocardial Function/Heart Failure---Basic/Molecular Presentation Number: 1070-73 Authors: Thor Ueland, Christen P. Dahl, Lars Gullestad, Pal Aukrust, Sven Aakhus, Kaspar Broch, Cees Vermeer, Leon J. Schurgers, Oslo University Hospital, Oslo, Norway, Maastricht University, Maastricht, The Netherlands Background: Matrix gla protein (MGP) is a calcification-inhibitor and MGP-deficient mice develop extensive vascular calcification resulting in severe hemodynamic changes and early death from congestive heart failure (HF). Moreover, MGP could contribute to myocardial remodelling through “calcification-independent” mechanisms such as their effects on matrix remodelling. We hypothesized that patients with chronic HF would have dysregulated circulating MGP levels. Methods: We investigated circulating (by enzyme immunoassay) uncarboxylated MGP (dp-ucMGP) in patients with HF and investigated associations with clinical and biochemical measures of HF as well as associations with mortality/HTx. Results: Plasma dp-ucMGP was markedly increased in patients (n=181) compared to healthy controls (n=92) with increasing levels according to etiology (increased in ischemic disease, p=0.004) and functional (NYHA, p=0.001), hemodynamic (correlation LVEF, r=-0.25, p=0.002; WMSI, r=0.28, p=0.001), and neurohormonal disease severity (correlation NTproBNP, r=0.40, p<0.001). Further, when investigating associations with mortality, non-survivors or patients who underwent HTx during a follow-up of 3.1±1.5 (mean±SD) years, had increased plasma levels compared to survivors (p=0.043). Survival analysis revealed a significantly higher mortality/HTx rate in the highest quartile of dp-ucMGP [HR 1.85 (1.01-3.38), p=0.045]. The activation of MGP is highly vitamin K dependent and adjusting for the use of vitamin K antagonists in multi-variable analyses, with dpucMGP as a continuous variable, still revealed predictive information for risk estimation. However, no predictive information for the risk estimation of was observed beyond demographic, clinical and biochemical variables (LVEF, NYHA class, etiology, age, sex, previous infarction, serum creatinine, LDL cholestrol and NTproBNP). Conclusion: Our data suggest a potential role for dp-ucMGP in the development of left ventricular dysfunction that should be further investigated.